Table 2.

Detailed energy breakdowns of computed CDK8-pyrazolourea ligands binding free energies ΔG_calc, along with experimental binding free energies, ΔG_exp. Change in mean energy associated with force-field bond-stretch, angle-bend and dihedral terms (ΔE_Valence); change in mean force-field Coulombic energy (ΔE_Coulomb); change in mean Poisson-Boltzmann solvation energy (ΔE_PB); change in mean nonpolar surface energy (ΔE_NP); change in mean force-field Lennard-Jones energy (ΔE_VDW); change in mean total energy ΔH, the sum of the prior five terms; and change in configurational entropy contribution to the free energy (−TΔS). Unit is kcal/mol. RMSD: root-mean-square deviation of most stable computed conformation of the complex for ligand alone/all mobile atoms (Angstroms).

ligand	ΔEValence	ΔECoulomb	ΔEPB	ΔENP	ΔEVDW	ΔH	−TΔS	ΔGcalc	ΔGexp	RMSD
1	1.031	−19.845	60.764	−8.548	−93.837	−60.435	39.487	−20.948	−10.324	1.457/1.753
2	1.498	−15.235	39.754	−6.577	−68.517	−49.077	30.610	−18.467	−10.979	1.810/0.728
3	2.338	−20.051	36.290	−4.754	−52.065	−38.242	28.983	−9.259	−7.184	1.727/0.600
4	2.217	−16.014	41.236	−5.760	−63.637	−41.958	26.605	−15.353	−7.877	1.637/1.318
5	2.065	−14.742	38.291	−5.760	−62.614	−42.760	28.792	−13.968	−8.447	1.851/2.492
6	2.512	−6.755	25.610	−3.652	−45.295	−27.580	21.130	−6.450	No bind
7	1.448	−14.167	31.055	−4.049	−49.417	−35.130	23.157	−11.973	−7.533	1.841/0.414
8	2.911	−16.977	33.393	−4.265	−53.090	−38.028	24.416	−13.612	−7.965
9	2.409	−21.251	37.597	−4.978	−54.164	−40.387	31.244	−9.143	−7.482
10	4.992	−19.615	39.659	−5.191	−62.883	−43.038	32.392	−10.646	−8.078
11	1.566	−29.122	43.449	−5.654	−58.240	−48.001	33.962	−14.039	−9.739	1.675/0.318